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Vericiguat in patients with worsening chronic heart failure and preserved ejection fraction: results of the SOluble guanylate Cyclase stimulatoR in heArT failurE patientS with PRESERVED EF (SOCRATES-PRESERVED) study.

Abstract：

Aims:To determine tolerability and the optimal dose regimen of the soluble guanylate cyclase stimulator vericiguat in patients with chronic heart failure and preserved ejection fraction (HFpEF). Methods and results:SOCRATES-PRESERVED was a prospective, randomized, placebo-controlled double-blind, Phase 2b dose-finding study in patients with HFpEF (ejection fraction ≥ 45%). Patients received vericiguat once daily at 1.25 or 2.5 mg fixed doses, or 5 or 10 mg titrated from a 2.5 mg starting dose, or placebo for 12 weeks. The two primary endpoints were change from baseline in log-transformed N-terminal pro-B-type natriuretic peptide (NT-ProBNP) and left atrial volume (LAV) at 12 weeks. Patients (N = 477; 48% women; mean age 73 ± 10 years; baseline atrial fibrillation 40%) were randomized within 4 weeks of HF hospitalization (75%) or outpatient treatment with intravenous diuretics for HF (25%) to vericiguat (n = 384) or placebo (n = 93). In the pooled three highest dose arms change in logNT-proBNP (vericiguat: +0.038 ± 0.782 log(pg/mL), n = 195; placebo: -0.098 ± 0.778 log(pg/mL), n = 73; one-sided P = 0.8991, two-sided P = 0.2017), and change in LAV [vericiguat: -1.7 ± 12.8 mL (n = 194); placebo: -3.4 ± 12.7 mL (n = 67), one-sided P = 0.8156, two-sided P = 0.3688] were not different from placebo. Vericiguat was well tolerated (adverse events: vericiguat 10 mg arm, 69.8%; placebo, 73.1%), with low discontinuation rates in all groups, and no changes in blood pressure at 10 mg compared with placebo. The pre-specified exploratory endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score improved in the vericiguat 10 mg arm by mean 19.3 ± 16.3 points [median 19.8 (interquartile range 10.4-30.7)] from baseline (mean difference from placebo 9.2 points). Conclusion:Vericiguat was well tolerated, did not change NT-proBNP and LAV at 12 weeks compared with placebo but was associated with improvements in quality of life in patients with HFpEF. Given the encouraging results on quality of life, the effects of vericiguat in patients with HFpEF warrant further study, possibly with higher doses, longer follow-up and additional endpoints.

journal_name

Eur Heart J

journal_title

European heart journal

authors

Pieske B,Maggioni AP,Lam CSP,Pieske-Kraigher E,Filippatos G,Butler J,Ponikowski P,Shah SJ,Solomon SD,Scalise AV,Mueller K,Roessig L,Gheorghiade M

doi

10.1093/eurheartj/ehw593

subject

Has Abstract

pub_date

2017-04-14 00:00:00

pages

1119-1127

issue

eissn

0195-668X

issn

1522-9645

pii

3078053

journal_volume

pub_type

杂志文章,多中心研究,随机对照试验

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Vericiguat in patients with worsening chronic heart failure and preserved ejection fraction: results of the SOluble guanylate Cyclase stimulatoR in heArT failurE patientS with PRESERVED EF (SOCRATES-PRESERVED) study.